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The misleading "smoker's paradox"

An article from the e-journal of the ESC Council for Cardiology Practice

Smoking is a strong risk factor for premature atherosclerosis, atherothrombotic events and cardio-vascular death. Curiously, smokers with acute myocardial infarction have lower short-term mortality rates than nonsmokers. The “smoker’s paradox” can be explained by differences in baseline risk factors, and not smoking status per se, mainly because smokers suffer their myocardial infarctions on average a decade earlier than nonsmokers.


Adverse cardiovascular effects of smoking

Cigarette smoking adversely affects the cardiovascular system via several mechanisms: hydrocarbons in smoke injure the arterial endothelium, promote low-grade inflammation and increase plasma fibrinogen, stimulate platelet aggregation and accelerate atherosclerosis; nicotine is associated with catecholamine release, which increases heart rate, raises arterial blood pressure, causes vasoconstriction and predisposes to cardiac arrhythmias; smoking also increases the level of carbon monoxide in blood which reduces myocardial oxygen delivery (1, 2). Smoking is strongly linked to peripheral arterial disease, myocardial infarction and sudden cardiac death (2).

Smoking status and early survival in acute myocardial infarction

During the past 20 years it has been consistently reported that smokers who suffer acute myocardial infarction (AMI) have a more favorable short-term prognosis than non-smokers. In the “thrombolytic treatment era” it had been postulated that the better response to thrombolysis in smokers was due to the more frequent thrombotic nature of coronary artery occlusion, presumably caused by a smoking-related hypercoagulable state, in contrast with the often more critical residual coronary stenoses found in non-smokers (1, 3). The crude in-hospital mortality of AMI treated with thrombolysis ranged from 2.3 – 4.7 % in smokers, to 5.2 – 7.6 % in former smokers, and to 7.0 – 13.8 % in non-smokers (1, 3-5).

In the “percutaneous coronary intervention treatment era” smokers with AMI have seemingly retained their survival advantage over former smokers and non-smokers with crude 30-day mortality rates of 1.3 % vs. 1.7 % vs. 3.5 % (6). However, after multivariate correction for differences in baseline variables smoking status was no longer protective from mortality: smokers were more than 10 years younger than non-smokers and had significantly lower rates of several factors that negatively affect prognosis – such as diabetes,  hypertension, triple-vessel disease,  left anterior descending coronary artery involvement, and being female (6).

It is noteworthy that the procedural success rates of percutaneous coronary intervention were similar in all groups in contrast to thrombolytic studies showing greater recanalization rates in smokers, attributed to the greater thrombus burden (6).

Baseline differences between smokers and nonsmokers with AMI

Already 20 years ago, a careful study of 2955 patients with AMI called attention to the fact that smokers were about a decade younger than non-smokers, had a lower prevalence of hypertension, congestive heart failure and diabetes, which made smoking an unlikely independent predictor of death in AMI (7). Although a very large study of more than 500 000 cases of AMI could not entirely explain the lower in-hospital mortality of smokers by the measured covariates (8), it is quite clear that smoking does not offer protection in the context of AMI, but rather that smokers suffer myocardial infarction at a significantly younger age than non-smokers with an otherwise similar risk-adjusted prognosis (4-7, 9, 10).

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.


The use of terms such as “smoker’s paradox” or “paradoxically beneficial effects of smoking on the early outcome of AMI” should be avoided, especially because they are misleading to the lay public. In fact, stopping smoking after AMI reduces the risk of death in the subsequent  2 – 10 years by almost one half in comparison with persistent smokers: in a meta-analysis of 12 studies the combined odds ratio was 0.54 with a 95 % confidence interval of 0.46-0.62 (11).  Health care professionals should continue their efforts in promoting non-smoking lifestyle and assisting in smoking cessation. 


1. Grines CL, Topol EJ, O’Neil WW, George BS, Kereiakes D, Phillips HR, et al. Effect of cigarette smoking on outcome after thrombolytic therapy for myocardial infarction. Circulation 1995; 91: 298-303.

2. Chen Z, Boreham J. Smoking and cardiovascular disease. Semin Vasc Med 2002; 2: 243-52.

3. Zahger D, Cercek B, Cannon CP, Jordan M, Davis V, Braunwald E, Shah PK. How do smokers differ from non-smokers in their response to thrombolysis? (the TIMI-4 trial). Am J Cardiol 1995; 75: 232-6.

4. Barbash GI, Reiner J, White HD, Wilcox RG, Armstrong PW, Sadowski Z, et al. Evaluation of paradoxic beneficial effects of smoking in patients receiving thrombolytic therapy for acute myocardial infarction: mechanism of the “smoker’s paradox” from the GUSTO-1 trial with angiographic insights. J Am Coll Cardiol 1995; 26: 1222-9.

5. Maggioni AP, Piantadosi F, Tognoni G, Santoro E, Franzosi MG. Smoking is not a protective factor in patients with acute myocardial infarction. The viewpoint of the GISSI-2 study. G Ital Cardiol 1998; 28: 970-8.

6. Weisz G, Cox DA, Garcia E, Tcheng JE, Griffin JJ, Guagliumi G, et al. Impact of smoking status on outcomes of primary coronary intervention for acute myocardial infarction – the smoker’s paradox revisited. Am Heart J 2005; 150: 358-64.

7. Kelly TL, Gilpin E, Ahnve S, Henning H, Ross J Jr. Smoking status at the time of acute myocardial infarction and subsequent prognosis. Am Heart J 1985; 110: 535-41.

8. Gourlay SG, Rundle AC, Barron HV. Smoking and mortality following acute myocardial infarction: results from the National Registry of Myocardial Infarction 2 (NMRI 2). Nicotine Tob Res 2002; 4: 101-7.

9. Gottlieb S, Boyko V, Zahger D, Balkin J, Hod H, Pelled B, Stern S, Behar S. Smoking and prognosis after acute myocardial infarction in the thrombolytic era (Israeli Thrombolytic National Survey). J Am Coll Cardiol 1996; 28: 1506-13.

10. Andrikopoulos GK, Richter DJ, Dilaveris PE, Pipilis A, Zaharoulis A, Gialafos JE, et al. In-hospital mortality of habitual cigarette smokers after acute myocardial infarction. The “smokers paradox” in a countrywide study. Eur Heart J 2001; 22: 776-84.

11. Wilson K, Gibson N, Willan A, Look D. Effect of smoking cessation on mortality after myocardial infarction: a meta analysis of cohort studies. Ann Intern Med 2000; 160: 939-44.


Vol4 N°15

Notes to editor

Prof. A. Blinc
Ljubljana, Slovenia
Nucleus Member of the Working group on Peripheral Circulation

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.